2014
Inverse Agonism of SQ 29,548 and Ramatroban on Thromboxane A2 Receptor
Chakraborty R, Bhullar RP, Dakshinamurti S, Hwa J, Chelikani P. Inverse Agonism of SQ 29,548 and Ramatroban on Thromboxane A2 Receptor. PLOS ONE 2014, 9: e85937. PMID: 24465800, PMCID: PMC3900440, DOI: 10.1371/journal.pone.0085937.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionBlood PlateletsBridged Bicyclo Compounds, HeterocyclicCalcium SignalingCarbazolesDrug Evaluation, PreclinicalFatty Acids, UnsaturatedHEK293 CellsHumansHydrazinesInositol 1,4,5-TrisphosphateMutagenesis, Site-DirectedReceptors, Thromboxane A2, Prostaglandin H2SulfonamidesConceptsThromboxane A2 receptorG protein-coupled receptorsA2 receptorsBasal activityPathophysiological conditionsImportant pathophysiological roleInverse agonist propertiesHuman platelet functionSuch constitutive activityTP dysfunctionConstitutive activityPlatelet hyperactivityProtein-coupled receptorsCardiovascular diseaseThromboxane A2Pathophysiological roleT cellsPlatelet functionImportant therapeutic applicationsAgonist propertiesRamatrobanPlatelet activationInverse agonistInverse agonismNeutral antagonists
2013
New Insights into Structural Determinants for Prostanoid Thromboxane A2 Receptor- and Prostacyclin Receptor-G Protein Coupling
Chakraborty R, Pydi SP, Gleim S, Bhullar RP, Hwa J, Dakshinamurti S, Chelikani P. New Insights into Structural Determinants for Prostanoid Thromboxane A2 Receptor- and Prostacyclin Receptor-G Protein Coupling. Molecular And Cellular Biology 2013, 33: 184-193. PMID: 23109431, PMCID: PMC3554117, DOI: 10.1128/mcb.00725-12.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCalciumFluorescent Antibody TechniqueGTP-Binding ProteinsHEK293 CellsHumansInositol 1,4,5-TrisphosphateLigandsModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNonlinear DynamicsProtein BindingProtein ConformationReceptors, EpoprostenolReceptors, Thromboxane A2, Prostaglandin H2Signal TransductionConceptsG protein-coupled receptorsG protein specificityThromboxane A2 receptorProtein interactionsProtein specificityIntracellular loopChimeric receptorsG proteinsGPCR-G protein interactionsProtein couplingHeterotrimeric G proteinsCognate G-proteinSite-directed mutagenesisNew molecular insightsProtein-coupled receptorsG protein couplingReceptor-G protein interactionG protein activationA2 receptorsReceptor-G protein couplingStructural basisMolecular insightsProtein activationMolecular natureStructural determinants
2012
Site-Directed Mutations and the Polymorphic Variant Ala160Thr in the Human Thromboxane Receptor Uncover a Structural Role for Transmembrane Helix 4
Chakraborty R, Pydi SP, Gleim S, Dakshinamurti S, Hwa J, Chelikani P. Site-Directed Mutations and the Polymorphic Variant Ala160Thr in the Human Thromboxane Receptor Uncover a Structural Role for Transmembrane Helix 4. PLOS ONE 2012, 7: e29996. PMID: 22272267, PMCID: PMC3260207, DOI: 10.1371/journal.pone.0029996.Peer-Reviewed Original ResearchMeSH Keywords15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAlanineAmino Acid SequenceAnimalsBinding SitesBinding, CompetitiveBridged Bicyclo Compounds, HeterocyclicCalciumChlorocebus aethiopsCOS CellsFatty Acids, UnsaturatedGlycineHEK293 CellsHumansHydrazinesMicroscopy, FluorescenceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedMutant ProteinsMutation, MissensePolymorphism, Single NucleotideProtein Structure, SecondaryRadioligand AssayReceptors, Thromboxane A2, Prostaglandin H2Structure-Activity RelationshipTemperature